Antiarrhythmic agents's tag archives

A question arises as to the possible clinical significance of cardiac ICa,L block by flecainide. Despite its efficacy in the treatment of some arrhythmias, the results of the Cardiac Arrhythmia Suppression Trial (CAST) showed that flecainide is associated with an increased patient mortality rate . The exact reason for this is unknown, but it may […]

To our knowledge, the precise binding site or sites for fle-cainide on the L-type channel in cardiac cells have not yet been determined. In recent experiments using cloned neuronal calcium channel subunits, Zamponi et al investigated ICa,L block by flecainide and the structurally related compound fomocaine. By changing the concentration of barium (the permeant ion […]

Using a protocol similar to that devised by Lee and Tsien to investigate the type of block of ICa,L by flecainide, we observed significant tonic block with a large drug concentration (1 mM) but not at 100 pM. This suggests that, in the AVN under our experimental conditions, binding of fle-cainide to the resting L-type […]

Scamps et al reported a EC50 (concentration of drug evoking a half maximal effect) of 20 pM and a Hill coefficient near 2, while our data suggest a Kd value in AVN cells near 60 pM and a Hill coefficient of 1.3. Our data suggest that, in rabbit AVN, the sensitivity of ICa,L to flecainide […]

DISCUSSION The principal finding of this study was that flecainide can inhibit ICa,L in isolated rabbit AVN myocytes. Relatively few studies have investigated the actions of flecainide on ICa,L, and this is the first study to characterize the actions of flecainide on any membrane current in the AVN. Class I anti-arrhythmics are thought to exert […]

The type of blocking action of Ica,L by flecainide was also investigated. A protocol similar to that described by Lee and Tsien and Delgado et al was used to investigate tonic- and use-dependence of the block. Test pulses were applied to +10 mV continuously in normal Tyrode’s solution to obtain control ICa,L amplitude, then pulsing […]

Figure 5A shows the results obtained with flecainide 1 mM (Figure 5Ai shows individual records from a single cell and Figure 5Aii the mean data from four cells). It is clear that the ICa,L elicited by the first pulse on resuming stimulation declined to 10% of the control amplitude and then showed a further decline […]